Anti-TGF-β improves bone architecture without detectable restoration of cortical bone lamellar nanomechanical organization in Col1a1+/- osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is characterized by impaired bone mechanical integrity and increased fracture risk. Although anti-transforming growth factor beta (anti-TGF-β) treatment improves bone architecture and whole-bone mechanical properties in Col1a1+/- OI mice, its effects on tissue-scale strain behavior and local cortical mechanics remain unclear. Here, digital volume correlation (DVC), atomic force microscopy (AFM), and Raman spectroscopy were used to assess tissue-scale strain distributions, local cortical mechanical organization, and matrix composition following 8 weeks of anti-TGF-β treatment. Treatment improved trabecular microarchitecture but produced no statistically detectable differences in tissue-scale strain distributions. AFM revealed distinct responses across lamellar structural contexts: periodicity strength of local apparent elastic modulus in parallel lamellar regions differed significantly by genotype, whereas concentric lamellar regions showed a significant genotype × antibody treatment interaction without significant main effects. Raman spectroscopy showed no significant differences in mineral- or matrix-related compositional parameters among groups. Exploratory anatomically matched AFM-Raman analyses suggested differences in composition-mechanics relationships among groups. Together, these findings indicate that improvements in bone architecture can occur without uniform changes in tissue-scale strain behavior or local cortical nanomechanical organization, highlighting the importance of multiscale assessment of bone quality following therapeutic intervention.